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Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the –OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer–Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer., Ministerio de Ciencia e Innovación, Universidad Complutense de Madrid, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, Instituto Universitario de Farmacia Industrial, TRUE, pub, Descuento UCM

Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90–95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.

Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH3+) and an increase in intramolecular hydrogen bonds, which were correlated with a high expansion of the interpolymer chains and an increase in the SIM dissolution rate. Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer–Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs., Ministerio de Ciencia e Innovación, España., Universidad Complutense de Madrid, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

Atorvastatin is a potent lipid-lowering drug with poor solubility and high presystemic clearance that limits its therapeutic efficacy. The aim of this study was to develop solid dispersions and micellar systems to obtain fast -dissolving atorvastatin systems that enhances their anti-hyperlipidemic effect. Solubility and wettability studies allow the development of solid dispersions with low proportions of croscarmellose sodium as hydrophilic carrier. Solid state characterization studies indicated that the addition of Kolliphor (R) RH40 surfactant to solid dispersions increases intermolecular hydrogen bonding between drug and polymer chains. Dissolution studies in biorelevant Fasted State Simulate Intestinal Fluid (FaSSIF pH 6.5) medium showed for atorvastatin solid dispersion a su-persaturation peak of atorvastatin followed by an aggregation/precipitation process. Only the presence of a surfactant such as Kolliphor (R) RH40 in atorvastatin micellar system, promotes the presence of micelles that achieve delayed recrystallization. Efficacy studies were carried out using a hyperlipidemic model of rats fed with a high-fat diet. The atorvastatin micellar system at doses of 10 mg/kg, revealed a significant improvement in serum levels of total cholesterol, low-density lipoproteins, and triglycerides compared to atorvastatin raw ma-terial. This micellar system also exhibited more beneficial effects on liver steatosis, inflammation and ballooning injury., Universidad Complutense de Madrid, Ministerio de Ciencia e Innovación de España., Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

Antecedentes: el mebendazol (MBZ) es un fármaco extremadamente insoluble y, por lo tanto, poco absorbido y los resultados clínicos variables pueden correlacionarse con las concentraciones sanguíneas. La necesidad de un tratamiento prolongado con dosis altas de este fármaco aumenta el riesgo de efectos adversos. Métodos: En el presente estudio preparamos micropartículas redispersables (RDM) que contienen MBZ, un fármaco oral poco soluble en agua, en diferentes proporciones de hidroxipropilcelulosa poco sustituida (L-HPC). Investigamos las estructuras de micropartículas que emergen espontáneamente tras la dispersión de un RDM en medio acuoso y dilucidamos su influencia en la disolución, y también en su biodisponibilidad oral y eficiencia terapéutica utilizando un modelo murino de infección con el parásito nematodo Trichinella espiralis. Resultados: Se obtuvieron porcentajes elevados de fármaco disuelto con RDM en proporciones 1:2,5 y 1:5 de MBZ:L-HPC. El análisis térmico mostró una amorfización de MBZ en el RDM por la ausencia de un pico de fusión claro de MBZ en las formulaciones. El rápido comportamiento de disolución podría deberse a la disminución de la cristalinidad del fármaco, el rápido tiempo de disolución de portadores como L-HPC, junto con su superior dispersabilidad y excelentes propiedades humectantes. RDM-1:2,5 y RDM-1:5 dieron como resultado un aumento de la concentración plasmática máxima y de los valores de área(s) bajo la curva (AUC)(0-infinito). Asimismo, después de la administración oral de RDM-1:2,5 y RDM-1:5, el AUC(0-infinito) fue 2,67 y 2,97 veces mayor, respectivamente, en comparación con el MBZ puro. La actividad terapéutica, evaluada en el ciclo de vida de Trichinella espiralis, mostró que RDM-1:5 fue el más eficaz para reducir el número de parásitos (4,56 veces) en comparación con el MBZ puro, en estado enquistado. Conclusión: El MBZ: L-HPC RDM podría ser una forma efectiva de mejorar la biodisponibilidad oral y la actividad terapéutica util, Background: Mebendazole (MBZ) is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects. Methods: In the present study we prepared redispersible microparticles (RDM) containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC). We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis. Results: Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage. Conclusion: The MBZ: L-HPC RDM might be an effective way of improving oral bioavailability and therapeutic activity using low doses of MBZ (5 mg/kg), which implies a low degree of toxicity for humans., Universidad Complutense de Madrid, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

Atorvastatin is a potent lipid-lowering drug with poor solubility and high presystemic clearance that limits its therapeutic efficacy. The aim of this study was to develop solid dispersions and micellar systems to obtain fastdissolving atorvastatin systems that enhances their anti hyperlipidemic effect. Solubility and wettability studies allow the development of solid dispersions with low proportions of croscarmellose sodium as hydrophilic carrier. Solid state characterization studies indicated that the addition of Kolliphor® RH40 surfactant to solid dispersions increases intermolecular hydrogen bonding between drug and polymer chains. Dissolution studies in biorelevant Fasted State Simulate Intestinal Fluid (FaSSIF pH 6.5) medium showed for atorvastatin solid dispersion a supersaturation peak of atorvastatin followed by an aggregation/precipitation process. Only the presence of a surfactant such as Kolliphor® RH40 in atorvastatin micellar system, promotes the presence of micelles that achieve delayed recrystallization. Efficacy studies were carried out using a hyperlipidemic model of rats fed with a high- fat diet. The atorvastatin micellar system at doses of 10 mg/kg, revealed a significant improvement in serum levels of total cholesterol, low-density lipoproteins, and triglycerides compared to atorvastatin raw material. This micellar system also exhibited more beneficial effects on liver steatosis, inflammation and ballooning injury., Ministerio de Ciencia e Innovacion (MICINN), Universidad Complutense de Madrid, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, inpress

Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia. El presente proyecto es continuación de un proyecto concedido con financiación el año 2019 y en él se continuarán desarrollando nuevos recursos educativos virtuales como los que ya se han hecho este curso, y que han tenido excelente acogida por los alumnos, para facilitar la adquisición del conocimiento de los estudiantes de Farmacia especialmente de aquellos temas en los que la bibliografía disponible es escasa como en el caso de la Asignatura de Tecnología Farmacéutica III en los temas dedicados a la industria farmacéutica.

The aim of this study was to develop multiparticulate systems with a combination of ezetimibe micellar systems and atorvastatin solid dispersions using croscarmellose as a hydrophilic vehicle and Kolliphor RH40 as a surfactant. The presence of a surfactant with low hydrophilic polymer ratios produces the rapid dissolution of ezetimibe through a drug–polymer interaction that reduces its crystallinity. The solid dispersion of atorvastatin with low proportions of croscarmellose showed drug–polymer interactions sufficient to produce the fast dissolution of atorvastatin. Efficacy studies were performed in diabetic Goto-Kakizaki rats with induced hyperlipidemia. The administration of multiparticulate systems of ezetimibe and atorvastatin at low (2 and 6.7 mg/kg) and high (3 and 10 mg/kg) doses showed similar improvements in levels of cholesterol, triglycerides, lipoproteins, alanine transaminase, and aspartate transaminase compared to the high-fat diet group. Multiparticulate systems at low doses (2 and 6.7 mg/kg of ezetimibe and atorvastatin) had a similar improvement in hepatic steatosis compared to the administration of ezetimibe and atorvastatin raw materials at high doses (3 and 10 mg/kg). These results confirm the effectiveness of solid dispersions with low doses of ezetimibe and atorvastatin to reduce high lipid levels and hepatic steatosis in diabetic rats fed a high-fat diet., Fundação para a Ciência e a Tecnologia, Portugal [PTDC/BIM-MET/4447/2014; POCI-01-0145-FEDER-016784], Ministerio de Ciencia e Innovación [MICINU, ref. RTI2018-093940-B-100], Universidad Complutense de Madrid (UCM) [Research Group 910939], Rafael Folch Foundation (Carlos Torrado-Salmerón acknowledges a grant awarded by the Rafael Folch Foundation), Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

The aim of this study was to improve the treatment of Candida albicans biofilms through the use of nystatin solid dispersions developed using maltodextrins as a hyperosmotic carrier. Characterization studies by differential scanning calorimetry, X-ray diffraction, dissolution studies, and particle size analysis were performed to evaluate changes in nystatin crystallinity. Antifungal activity and anti-biofilm efficacy were assessed by microbiological techniques. The results for nystatin solid dispersions showed that the enhancement of antifungal activity may be related to the high proportions of maltodextrins. Anti-biofilm assays showed a significant reduction (more than 80%) on biofilm formation with SD-N:MD [1:6] compared to the nystatin reference suspension. The elaboration process and physicochemical properties of SD-N:MD [1:6] could be a promising strategy for treatment of Candida biofilms., Ministerio de Ciencia e Innovación [MICINU], Faculty of Pharmacy, University Complutense of Madrid [Research Group 910939], Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

La migraña es una de las afecciones que más población padece en todo el mundo, por ese motivo, es de gran interés mejorar y/o desarrollar nuevos tratamientos que traten y ayuden a las personas que la sufren. Actualmente los tratamientos se pueden dividir en 2 modalidades: los tratamientos agudos y los tratamientos profilácticos. Existen multitud de medicamentos para tratar estas modalidades, pero los que aparecen indicados en ambas, son los AINES. Dentro de los AINES, el naproxeno es el que mejores características reúne para intentar perfeccionar su formulación. Las razones principales para centrarse en el naproxeno son dos. La primera es su gran uso generalizado; y la segunda es su posible margen de mejora, esto es debido tanto a su alta dosis de inicio (1000mg), como a su lenta liberación (Tmax 2-4h). Por ello, lo que se pretende es tanto mejorar su biodisponibilidad, como el tiempo de efecto, disminuyendo así la dosis efectiva y el tiempo de actuación..., Migraine is one of the most worldwide-spread health conditions. Hence, it is of pronounced interest to improve current treatments and/or develop novel treatments that would improve patients’ health.Currently, treatments can be divided into 2 modalities based on the status of the condition: acute treatments, for ongoing migraine episodes, and prophylactic treatments, as preventive treatment. Out of the large group of medicines being used as treatment, NSAIDs products are commonly used at both modalities. Within NSAIDs products, naproxen’s characteristics has shown great feasibility when used for optimizing formulation.Naproxen has been selected due to two main reasons. Firstly, its widespread use; and secondly, its potential margin of improvement, as a result of both its high starting dose (1000mg), and its slow release (Tmax 2-4h). Thus, the aspiration would be to improve both its bioavailability and the time of effect, consequently decreasing the effective dose and the time of action...

Los niveles elevados de colesterol y las concentraciones anormales de algunos lípidos y lipoproteínas en sangre, se consideran factores de riesgo de enfermedades cardiovasculares y distintos síndromes metabólicos. El aumento de colesterol y lipoproteínas puede deberse a factores genéticos como la hipercolesterolemia familiar o la hiperlipidemia familiar combinada y factores externos como el tabaco, una disminución de la actividad física y una dieta rica en grasas saturadas. Una de las causas más frecuente de enfermedad cardiovascular es la aterosclerosis o enfermedad aterosclerótica vascular, que implica la formación de placas de ateroma constituidas por la acumulación de colesterol, triglicéridos, y otras sustancias que circulan por el torrente sanguíneo y quedan adheridas a las paredes de los vasos..., High cholesterol levels and abnormal concentrations of certain lipids and lipoproteins in blood are considered risk factors for cardiovascular diseases and a range of metabolic syndromes. Increases in cholesterol and lipoproteins may be caused by genetic factors such as familial hypercholesterolemia or familial combined hyperlipidemia and external factors such as smoking, a decline in physical activity and a diet high in saturated fats.One of the most frequent causes of cardiovascular disease is atherosclerosis or atherosclerotic cardiovascular disease, which involves the formation of atheromatous plaques due to the accumulation of cholesterol, triglycerides and other substances that circulate via the bloodstream and become adhered to the walls of the blood vessels...

La aspergilosis invasora (AI) es una micosis sistémica producida por hongos del género Aspergillus, siendo la especie patógena más común A. fumigatus. Por lo general los conidios alcanzan el organismo por inhalación y la enfermedad afecta en primer lugar a los pulmones. La AI se produce cuando la infección se disemina, lo que ocurre principalmente en individuos inmunocomprometidos, y está asociada con una elevada mortalidad. El tratamiento de elección de la AI es el voriconazol, sin embargo, su eficacia se ve limitada por su baja solubilidad en agua. Otro problema de este fármaco es su elevada hepatotoxicidad, que puede provocar la suspensión del tratamiento. Las limitaciones mencionadas se pueden resolver mediante la fabricación de dispersiones sólidas y sistemas micelares. Estas formulaciones tienen la propiedad de formar micelas en presencia de un medio acuoso, lo que proporciona ventajas como el aumento de la solubilidad, el incremento de la biodisponibilidad, la modificación en la biodistribución y la atenuación de la toxicidad..., Invasive aspergillosis (IA) is a systemic fungal infection caused by fungi of the genus Aspergillus, being A. fumigatus the most common pathogenic species. Conidia usually reach the body by inhalation, and the disease first affects the lungs. IA takes place when haematological dissemination occurs, which mainly happens in immunocompromised individuals, and it is associated with high mortality. Voriconazole is currently the first-line treatment for IA, however its effectiveness is limited by its low solubility in water. Another problem with this drug is its elevated hepatotoxicity, which can cause treatment discontinuation. These limitations can be overcome by manufacturing solid dispersions and micellar systems. These formulations have the property of forming micelles in the presence of an aqueous medim, which provides advantages such as increased solubility, risen bioavailability, modification in biodistribution and attenuation of toxicity...

La combinación de diferentes proporciones de chitosán (CS) y carboximetilcelulosa (CMC) permite desarrollar complejos polielectrolitos que nos permiten la liberación sostenida de fármacos. El objetivo de este estudio es crear comprimidos con diferentes proporciones de (CS) y (CMC) que permitan obtener diferentes perfiles de liberación sostenida de Claritromicina (CL). La (CL) es un antibiótico oral de amplio espectro pero que está en la primera línea de tratamiento para el Helicobacter pylori. La (CL) es poco soluble (Clase II) y su solubilidad depende del pH del medio. Los sistemas de liberación sostenida podrían mejorar la eficacia frente al tratamiento del Helicobacter pylori

Ezetimibe (EZ) is a poorly water-soluble drug with low bioavailability. Strategies such as solid dispersions (SD) and micellar systems (MS) were developed to identify the most effective drug delivery formulations with the highest oral bioavailability, and to improve their lipid-lowering effect. The EZ formulations were prepared with different proportions of Kolliphor® RH40 as a surfactant (1:0.25, 1:0.5 and 1:0.75) and croscarmellose as a hydrophilic carrier. These excipients, and the addition of microcrystalline cellulose during the production process, led to significant improvements in the dissolution profiles of MS. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) revealed an amorphous form of ezetimibe with different semicrystalline states of microcrystalline cellulose for MS-I (1:0.75) and MS-II (1:0.75). Pharmacokinetic analysis after administration of MS-II (1:0.75) demonstrated a 173.86% increase in maximum plasma concentration (Cmax) and a 142.99% increase in oral bioavailability compared to EZ raw material (EZ-RM). Efficacy studies with the micellar system MS-II (1:0.75) in rats with hyperlipidemia showed that total cholesterol, triglycerides and high-density lipoprotein were reduced to normal levels and revealed improvements in low-density lipoprotein, aspartate and alanine aminotransferase. The improvement in the dissolution rate with micellar systems increases bioavailability and enhances the anti-hyperlipidemic effect of EZ., Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

La aspergilosis invasora (AI) es una micosis sistémica producida por hongos del género Aspergillus, siendo la especie patógena más común A. fumigatus. Por lo general los conidios alcanzan el organismo por inhalación y la enfermedad afecta en primer lugar a los pulmones. La AI se produce cuando la infección se disemina, lo que ocurre principalmente en individuos inmunocomprometidos, y está asociada con una elevada mortalidad. El tratamiento de elección de la AI es el voriconazol, sin embargo, su eficacia se ve limitada por su baja solubilidad en agua. Otro problema de este fármaco es su elevada hepatotoxicidad, que puede provocar la suspensión del tratamiento. Las limitaciones mencionadas se pueden resolver mediante la fabricación de dispersiones sólidas y sistemas micelares. Estas formulaciones tienen la propiedad de formar micelas en presencia de un medio acuoso, lo que proporciona ventajas como el aumento de la solubilidad, el incremento de la biodisponibilidad, la modificación en la biodistribución y la atenuación de la toxicidad...

Los niveles elevados de colesterol y las concentraciones anormales de algunos lípidos y lipoproteínas en sangre, se consideran factores de riesgo de enfermedades cardiovasculares y distintos síndromes metabólicos. El aumento de colesterol y lipoproteínas puede deberse a factores genéticos como la hipercolesterolemia familiar o la hiperlipidemia familiar combinada y factores externos como el tabaco, una disminución de la actividad física y una dieta rica en grasas saturadas. Una de las causas más frecuente de enfermedad cardiovascular es la aterosclerosis o enfermedad aterosclerótica vascular, que implica la formación de placas de ateroma constituidas por la acumulación de colesterol, triglicéridos, y otras sustancias que circulan por el torrente sanguíneo y quedan adheridas a las paredes de los vasos...

La migraña es una de las afecciones que más población padece en todo el mundo, por ese motivo, es de gran interés mejorar y/o desarrollar nuevos tratamientos que traten y ayuden a las personas que la sufren. Actualmente los tratamientos se pueden dividir en 2 modalidades: los tratamientos agudos y los tratamientos profilácticos. Existen multitud de medicamentos para tratar estas modalidades, pero los que aparecen indicados en ambas, son los AINES. Dentro de los AINES, el naproxeno es el que mejores características reúne para intentar perfeccionar su formulación. Las razones principales para centrarse en el naproxeno son dos. La primera es su gran uso generalizado; y la segunda es su posible margen de mejora, esto es debido tanto a su alta dosis de inicio (1000mg), como a su lenta liberación (Tmax 2-4h). Por ello, lo que se pretende es tanto mejorar su biodisponibilidad, como el tiempo de efecto, disminuyendo así la dosis efectiva y el tiempo de actuación...

Scientists have explored different manufacturing methods aiming at obtaining synthetic materials with controlled porosity, among them, Freeze Casting allows a control of the pore characteristics formed within the material by setting process variables like type of medium, particle size, solid content, inclusion of additives, freezing rate, etc. Despite of all the knowledge obtained about freeze casting, there still remain some questions to solve regarding processing-structure relationships, specifically the relations between cooling patterns during freezing and physical characteristics of the final material. The aim of this doctoral work is to understand the relations between cooling patterns during freezing and the structure at the macro and micro levels of the final freeze casted part. The current work comprises the development of a heat transfer model to efficiently and reliably predict the temperature evolution during freezing. In this way, it will be possible to recognize which are the process variables affecting the final pore morphology. The results of this work improved the fundamental knowledge of the process, serving as a tool to predict and control the microstructure obtained in the Freeze Casting process. The problem definition and goals of this work are presented in chapter 1. A brief description of the main literature on freeze casting is presented in chapter 2. The development of a numerical model that calculates the temperature distribution within the experiment domain was carried out in chapter 3. In chapter 4, an alumina tile was produced by freeze casting process in order to test the freezing device, coloidal suspension characteristics and sintering temperature of the sample. Additionally, an analytical model was proposed for predicting the thermal conductivity of the material. Chapter 5 evaluates the effect of solid content and freezing temperature on pore morphology and evaluates how these variables affect the temperature distribution within the

The aim of this work was to develop ezetimibe self-micellizing solid dispersions using Kolliphor® RH40 (MS-K) as a surfactant incorporating ezetimibe (EZ) into the croscarmellose hydrophilic carrier. Different ezetimibe:Kolliphor® ratios were studied to select micellar systems that improve the dissolution properties of ezetimibe. The different formulations were characterized by means of solid state analysis by SEM, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and dissolution studies. These physicochemical studies showed a decrease from the crystalline structure of ezetimibe (EZ) to its amorphous state in the micellar systems (MS-K). A rapid dissolution profile was observed in these micellar systems compared to the drug raw material and physical mixture. Efficacy studies were conducted using a high-fat diet that induced hyperlipidemic rats. The micellar system selected (MS-K 1:0.75) revealed a significant improvement in serum levels of total cholesterol (TC), low-density lipoproteins (LDL), and triglycerides (TG) compared to ezetimibe raw material. The histopathological examination of liver tissue also showed that this micellar system exhibited more beneficial effects on liver steatosis compared to ezetimibe raw material (EZ-RM) and the high-fat diet group (HFD). This study suggests that EZ micellar systems using Kolliphor® RH40 could enhance the antihyperlipidemic effect of ezetimibe and reduce liver steatosis., Ministerio de Ciencia e Innovación (MICINN), Universidad de Madrid, Rafael Folch Foundation (Carlos Torrado-Salmerón acknowledges a grant awarded by the Rafael Folch Foundation), Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

La infección de la mucosa oral por Candida albicans es una patología creciente a nivel mundial debido al gran número de pacientes inmunodeprimidos, hospitalizados de larga duración o que requieren dispositivos de uso clínico. Aunque en pacientes sanos, estas infecciones suelen ser autolimitantes, en pacientes con el sistema inmune comprometido pueden llegar a constituir un grave problema de salud debido a la capacidad de desarrollar resistencias, la dificultad en el manejo de la infección y la formación de biopelículas por parte del hongo, que impiden la penetración del compuesto antifúngico. De hecho, estas biopelículas son un factor de mal pronóstico en enfermos intubados o cateterizados. Nistatina, un antifúngico polieno muy conocido, con un adecuado perfil de actividad antifúngica y asequible económicamente ha demostrado tener capacidad inhibitoria del desarrollo de estas biopelículas y puede constituir una excelente elección como tratamiento de la candidiasis oral...

Creación de un nuevo recurso educativo virtual para estudiantes de grado en Farmacia sobre la serialización de los medicamentos y los procesos de mezclado.

La infección de la mucosa oral por Candida albicans es una patología creciente a nivel mundial debido al gran número de pacientes inmunodeprimidos, hospitalizados de larga duración o que requieren dispositivos de uso clínico. Aunque en pacientes sanos, estas infecciones suelen ser autolimitantes, en pacientes con el sistema inmune comprometido pueden llegar a constituir un grave problema de salud debido a la capacidad de desarrollar resistencias, la dificultad en el manejo de la infección y la formación de biopelículas por parte del hongo, que impiden la penetración del compuesto antifúngico. De hecho, estas biopelículas son un factor de mal pronóstico en enfermos intubados o cateterizados. Nistatina, un antifúngico polieno muy conocido, con un adecuado perfil de actividad antifúngica y asequible económicamente ha demostrado tener capacidad inhibitoria del desarrollo de estas biopelículas y puede constituir una excelente elección como tratamiento de la candidiasis oral..., The infection of the oral mucosa by Candida albicans is a growing pathology worldwide due to the large number of immunosuppressed patients, long-term hospitalizations or patients requiring clinical devices. Although in healthy patients, these infections are usually self-limiting, in patients with compromised immune system can become a serious problem because of the ability to develop resistances, the difficulty in handling the infection and the formation of biofilms by the fungus, which prevent the penetration of the antifungal compound. In fact, these biofilms are a factor of poor prognosis in intubated or catheterized patients. Nystatin, a well-known polyene antifungal, with an adequate profile of antifungal activity and economically available, has an inhibitory effect for the development of these biofilms and can be an excellent choice as a treatment for oral candidiasis...

En los últimos años, las infecciones fúngicas invasivas (IFIs), en concreto las candidiasis, causan una elevada morbilidad y mortalidad tras la realización de trasplantes pulmonares. Por otro lado, diferentes especies de Aspergillus han emergido como una de las causas más importantes de mortalidad y morbilidad en pacientes inmunocomprometidos. El principal foco de infección de este tipo de infecciones fúngicas en humanos es el pulmón, con diseminación en otros órganos, a medida que la enfermedad progresa. Para un tratamiento eficaz de la aspergilosis pulmonar es necesario alcanzar elevadas concentraciones pulmonares de anfotericina B. Las bajas concentraciones pulmonares en las primeras 48 horas de la formulación liposomal de anfotericina B unido a sus altos costes, limitan su uso. Por otro lado, la formulación comercial dimérica deanfotericina B con desoxicolato sódico presenta menor eficacia y causa una elevada nefrotoxicidad. Debido a todo esto, es necesario encontrar nuevas formulaciones de anfotericina B, como son sistemas poliagregados deanfotericina B con desoxicolato sódico que garanticen mayor eficacia frente a agentes patógenos pulmonares..., In recent years, invasive fungal infections (IFIs), especially candidiasis, cause high morbidity and mortality after lung-transplant. On the other hand, different Aspergillus species have emerged as one of the main cause of mortality and morbidity in immunosuppressed patients. The initial site of most fungal infections in humans is primarily the lungs, with dissemination to other organs as the disease progresses. So, it is important to reach high initial pulmonary concentrations of amphotericin B (AmB) in order to get an effective treatment. The high costs of commercial lipid formulations and the low pulmonary concentrations reached during the first 48 hours, limit their use. On the other hand, the less expensive commercial dimeric sodium deoxycholateamphotericin B formulation has lower antifungal efficacy and causes serious nephrotoxicity. Due to these reasons, it is necessary to find out new amphotericin B formulations, such as poly-aggregated systems of amphotericinB with sodium deoxycholate (DCH), that guarantee greater efficacy and lower toxicity than commercial formulations...

Manufacturing and assembly industries are constantly searching to optimize their resources and achieve improvements in their production systems. At a time when the differentiating factor is found in efficiency and competitiveness in production, lean manufacturing philosophy contributes to these differentiators, focusing mainly on the elimination of waste to obtain an improvement in the processes, quality and delivery times, being evident the results in a short period of time. This article proposes optimizing processes within a bicycle assembly plant by applying a lean manufacturing tool called Value Stream Map (VSM), which presents the sequence of production processes and requirements of each one, graphically reflecting the current situation and facilitating the identification of waste within the system. For illustrative purposes regarding process mapping, a bicycle model identified as E 26 was selected. Additionally, the tool 5 S that seeks to maintain tidiness and cleanliness within the processes for obtaining an agile production flow is used. The work also includes the balancing of lines, obtaining a reduction of 14% in cycle times and 66% in lead time, generating a mixed production (push and pull). In addition, a warehouse distribution of raw material, obtaining the unification of all the materials involved in the process. Finally, it was verified the validity of the future VSM through software of simulation of discrete events, being an important contribution in the study, obtaining validating the results obtained from the application of tools lean manufacturing.